“埃博拉”和“马尔堡”丝状病毒的超强致病性，促使人们对它们繁殖及致病的分子机制进行深入研究。
“埃博拉”丝状病毒
Carette等人利用人细胞中全基因组范围的基因筛选方法来识别“埃博拉”病毒的进入所需因子。该筛选发现了破坏“同型融合”和“液泡蛋白分拣”(HOPS) “多亚基系留复合物”（该复合物参与了内涵体向溶酶体的融合）的全部6个成员的67个突变，以及破坏“内涵体/溶酶体胆固醇运输蛋白” Niemann–Pick C1 (NPC1)的39个独立突变。
Côté等人发现了一种新的来自“benzylpiperazine adamantane diamide”的化合物，该化合物能在细胞培养中以NPC1为目标抑制“埃博拉病毒”(EboV)感染。遗传性致病基因NPC1在“埃博拉病毒”感染中所起的出乎意料的作用，可能会有助于抗丝状病毒治疗药物的开发。
生物探索推荐英文摘要
Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification. Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann–Pick C1 (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann–Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents.
